The axons of manly vertebrate neurons are insulated by a myelin sheath, which greatly increases the rate at which axons can conduct an action potential. Myelin is a cellular sheath formed by special glial cells, namely Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. These glial cells wrap layer upon layer around the axon in a tight spiral, thereby insulating the axonal membrane. However, the sheath is interrupted at regularly spaced nodes of Ranvier, where membrane depolarization can occur. As a result, depolarization of the membrane at one node immediately spreads to the next node. Thus, an action potential propagates along a myelinated axon by jumping from node to node, thereby accelerating transmission of the signal as well as conserving metabolic energy, since the active excitation is confined to the small regions of axonal plasma membrane at the nodes.
The importance of myelination is evidenced by demyelinating diseases such as multiple sclerosis, in which myelin sheaths in some regions of the central nervous system are destroyed by an unknown mechanism. When demyelination occurs, the propagation of nerve impulses is significantly slowed, leading to devastating neurological consequences. For example, common symptoms of multiple sclerosis include muscular weakness, slow movements, spasticity, severe fatigue or even disabling exhaustion, visual disturbances, pain, numbness, tingling, urinary dysfunction, sexual dysfunction and mental disturbances.
Current treatments of multiple sclerosis involve slowing down the disease course as well as alleviation of the symptoms or medical complications, rather than addressing the underlying cause of the disease, demyelination. Howsoever, ample evidence indicates that demyelinated neurons are capable of remyelination in siru. In multiple sclerosis, it appears that cycles of demyelination and remyelination take place, and glial cell transplantation has been investigated as a potential therapy (see, e.g., Smith et al., 2001; Brierley et al., 2001: Kohama et al., 2001). Nevertheless, obtaining large numbers of myelinating cells for transplantation remains a major stumbling block. Glial progenitor cells are available for transplantation; for example, O-2A cells give rise in vitro to oligodendrocytes and type II astrocytes. Although O-2A cells can be grown in culture, only a limited number of divisions are possible (Raff, 1989). Moreover, it appears that the O-2A cells that have been injected into animals do not continue to divide, and a large number of cells have to be transplanted. Therefore, an improved source of transplant for remyelination is desirable.